Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and anti-CD20 monoclonal antibodies Journal Article

Authors: Ma, D.; McDevitt, M. R.; Barendswaard, E.; Lai, L.; Curcio, M. J.; Pellegrini, V.; Brechbiel, M. W.; Scheinberg, D. A.
Article Title: Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and anti-CD20 monoclonal antibodies
Abstract: In recent years, radioimmunotherapy (RIT) with β- particle emitting radionuclides targeting the CD20 antigen on B cells in the treatment of non-Hodgkin's lymphoma has provided the most compelling human clinical data for the success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells of the B lineage, and CD19 may provide an alternative target for radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a target for conventional 131I RIT, because the antigen rapidly internalizes upon binding of antibody, resulting in catabolism and significant release of 131I. Such modulation may be an advantage to RIT with radiometals such as 90Y, 177Lu, 213Bi and 225Ac. Herein, we have compared β- particle RIT with antibodies targeting either CD19 or CD20. The anti-CD19 and anti-CD20 antibodies, B4 or C2B8, respectively, were appended with the SCN-CHX-A"-DTPA bifunctional chelating agent and labeled with 90Y. In the tumor model used, there were three times as many CD20 target sites on lymphoma cells as compared to CD19 sites (62 000 vs 20 000 binding sites, respectively). We compared the efficacy of the 90Y-labeled antibodies to reduce lymphoma in a nude mouse xenograft solid tumor model, after measurable lymphoma appeared. Reduction in tumor size began at day 3 in all three 90Y-treated groups, but tumor began to recur in many animals 9 days after the treatments. There was one cure in each specific treatment group. In contrast, the tumor in the two control groups showed no regression. There was a significant prolongation of median survival time from xenograft (P< 0.0001) in all the 90Y-labeled antibody construct-treated groups (32 days for 0.15 mCi 90Y-B4; 26 days for 0.20 mCi 90Y-C2B8, and 23 days for 0.15 mCi 90Y-C2B8) in comparison to the two control groups (11 days for 0.02 mg of C2B8 and 9 days for untreated growth controls). Specificity of the radioimmunotherapy was also shown. In conclusion, 90Y-labeled anti-CD20 antibody in the treatment of mice bearing human lymphoma xenografts. These data suggest that CD19-targeted RIT merits further study.
Keywords: controlled study; human tissue; unclassified drug; cancer recurrence; drug efficacy; nonhuman; radiation dose; rituximab; antigen expression; mouse; animals; mice; cancer immunotherapy; animal experiment; animal model; tumor xenograft; tumor cells, cultured; xenograft model antitumor assays; cancer model; b lymphocyte; cell lineage; monoclonal antibody; survival time; b cell lymphoma; cd20 antigen; cancer regression; antigens, cd20; antibodies, monoclonal; nonhodgkin lymphoma; antigens, neoplasm; iodine 131; isotope labeling; xenograft; nude mouse; mice, nude; non-hodgkin's lymphoma; cancer size; radioisotope; antigen binding; radioimmunotherapy; yttrium radioisotopes; cd19 antigen; burkitt lymphoma; antigens, cd19; antibody affinity; electron; cell surface; actinium; bismuth 213; lutetium; chelating agent; anti-cd20; b lymphocyte antigen; immunologic agent; monoclonal antibody cd19; 90y; humans; human; female; priority journal; article; anti-cd19; 2 (4 isothiocyanatobenzyl)diethylenetriaminepentaacetic acid; monoclonal antibody b4; monoclonal antibody c2b8; monoclonal antibody cd20; monoclonal antibody y 90
Journal Title: Leukemia
Volume: 16
Issue: 1
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2002-01-01
Start Page: 60
End Page: 66
Language: English
DOI: 10.1038/sj/leu/2402320
PUBMED: 11840264
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael R Mcdevitt
    132 Mcdevitt
  2. Dangshe Ma
    21 Ma
  3. Michael J Curcio
    28 Curcio
  4. Lawrence T Lai
    20 Lai